Bring a large pot of lightly salted water to a boil, then stir in pasta. Cook for 7 minutes then drain.

Melt the butter in a large saucepan over medium heat. Whisk in the flour. Continue whisking until the roux gently bubbles, about 2 minutes. Slowly add the milk, a little bit at a time, whisking until smooth between each addition. Once the roux forms a thin paste, whisk in the remaining milk. Bring the mixture to a boil over medium-high heat, then reduce to a simmer and cook for 10 minutes.

Remove the pot from the heat and add in the onion powder, garlic powder, cayenne pepper, salt and pepper.

Working with about one cup of cheese at a time, add a combination of the cheddar, asiago, and parmesan cheese to the mixture - Whisk until smooth between each addition. (reserve a small amount of cheese to sprinkle on top before baking)

Pour the cheese sauce over the cooked penne and mix well to coat the pasta.

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